AAV-intein ABCA4

AAV-intein ABCA4 is an experimental gene therapy developed by Aavantgarde Bio for the treatment of Stargardt disease (STGD1). Stargardt disease is caused by mutations in the ABCA4 gene, which encodes a large protein (~250 kDa) whose cDNA exceeds the ~4.7 kb packaging limit of standard adeno-associated virus (AAV) vectors. To overcome this, AAV-intein ABCA4 utilizes a dual-vector system based on AAV serotype 8. The system consists of two separate AAV8 vectors, one carrying the 5' portion and the other the 3' portion of the human ABCA4 coding sequence, each fused to a split-intein. When both vectors co-infect a retinal cell, the split-inteins mediate protein trans-splicing, resulting in the assembly of the full-length, functional ABCA4 protein. This approach is designed to restore the transport of retinoids in photoreceptors, addressing the underlying cause of vision loss in STGD1 patients.

Other names

adeno-associated virus serotype 8 vector containing the 5'-half coding sequence of human ABCA4 fused to an intein + adeno-associated virus serotype 8 vector containing the 3'-half coding sequence of human ABCA4 fused to an intein